SAMHD1 acts at stalled replication forks to prevent interferon induction

Investor logo
Investor logo

Warning

This publication doesn't include Faculty of Arts. It includes Faculty of Medicine. Official publication website can be found on muni.cz.
Authors

COQUEL Flavie SILVA Maria Joao TECHER Hervé ZADOROZHNY Karina SHARMA Sushma NIEMINUSZCZY Jadwiga METTLING Clément DARDILLAC Elodie BARTHE Antoine SCHMITZ Anne Lyne PROMONET Alexy CRIBIER Alexandra SARRAZIN Amélie NIEDZWIEDZ Wojciech LOPEZ Bernard COSTANZO Vincenzo KREJČÍ Lumír CHABES Andrei BENKIRANE Monsef YEA-LIH Lin PASERO Philippe

Year of publication 2018
Type Article in Periodical
Magazine / Source Nature
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.1038/s41586-018-0050-1
Keywords SAMHD1
Description SAMHD1 was previously characterized as a dNTPase that protects cells from viral infections. Mutations in SAMHD1 are implicated in cancer development and in a severe congenital inflammatory disease known as Aicardi-Goutieres syndrome. The mechanism by which SAMHD1 protects against cancer and chronic inflammation is unknown. Here we show that SAMHD1 promotes degradation of nascent DNA at stalled replication forks in human cell lines by stimulating the exonuclease activity of MRE11. This function activates the ATR-CHK1 checkpoint and allows the forks to restart replication. In SAMHD1-depleted cells, single-stranded DNA fragments are released from stalled forks and accumulate in the cytosol, where they activate the cGAS-STING pathway to induce expression of pro-inflammatory type I interferons. SAMHD1 is thus an important player in the replication stress response, which prevents chronic inflammation by limiting the release of single-stranded DNA from stalled replication forks.
Related projects:

You are running an old browser version. We recommend updating your browser to its latest version.